Project no. NVKP 16-1&#8211;2016-0017 (&#8217;National Heart Program&#8217;) has been implemented with the support provided by the National Research, Development, and Innovation Fund of Hungary, financed under the NVKP 16 funding scheme. The research was financed by the Thematic Excellence Programme (2020-4.1.1.-TKP2020) of the Ministry for Innovation and Technology in Hungary, within the framework of the Therapeutic Development and Bioimaging thematic programs of the Semmelweis University.&#160;

In the following part we describe the protocol steps of clinical and imaging evaluation of atrial communications before transcatheter closure based on international clinical guidelines. These protocols follow the guidelines of the Semmelweis University Regional and Institutional Committee of Science and Research Ethics. Informed written patient consent is needed.
1. Clinical evaluation and workflow of cryptogen stroke and PFO for transcatheter closure
<ol>
	<li>For the diagnostic work-up of stroke, determine whether the stroke is ischemic or hemorrhagic in origin using computed tomography scan (CT) or magnetic resonance brain imaging (MRI).&#160;</li>
	<li>In case of ischemic etiology, perform subsequent CT- or MR-angiography of the head and neck to exclude any intracranial- and cerebral- or extracerebral vascular pathology, which would warrant specific therapy.&#160;</li>
	<li>Perform blood work to test for a hypercoagulable state, most importantly an antiphospholipid syndrome or other genetic alterations leading to a coagulation disorder.&#160;A patient with hypercoagulability is not a good candidate for closure, as thrombus formation could occur on the surface or near the implanted device in these cases4,5.</li>
	<li>Use inpatient ECG monitoring to rule out atrial fibrillation. 
	NOTE: Further extended outpatient rhythm monitoring with an ambulatory 24-36-hour Holter, with an external event recorder or even with an insertable monitoring device, should be considered to detect the occurrence of atrial fibrillation, which is silent in a considerable proportion of stroke patients.</li>
	<li>Perform a TTE scan to exclude cardioembolic sources other than atrial fibrillation, such as non-compaction cardiomyopathy, dilated cardiomyopathy with severely depressed left ventricular ejection fraction, any intracardiac mass, vegetation or intracavitary thrombus and to assess the morphology of the interatrial septum for the presence of septal aneurysm. 
	NOTE: The latter can raise the suspicion for the presence of PFO.</li>
	<li>For the final work-up step in patient selection for PFO closure, make a multidisciplinary team decision involving the neurologist, the cardiologist and the cerebral imaging specialist.</li>
</ol>
2. Clinical evaluation and workflow of ASD for transcatheter closure
<ol>
	<li>Perform preprocedural cardiac MR (CMR) and right heart catheterisation (RHC) to diagnose complex congenital heart disease, where an ASD is only one element of a complex case. In these cases, closure of the ASD is usually part of a complex surgical repair procedure, rather than a transcatheter one.&#160; 
	NOTE: Simple, secundum type ASDs with a volume-overloaded RV due to a pulmonary/systemic flow (Qp/Qs) ratio of &#62;1.5 and not elevated RV pressure are suitable for a single-step transcatheter closure if surrounded by a minimum rim of 5 mm6. Multi-fenestrated defects are often amenable for closure with multiple devices.&#160;</li>
	<li>Measure pulmonary vascular resistance (PVR) at baseline by RHC when shunting is excessive and there is elevated RV systolic pressure.
	<ol>
		<li>In case of moderately elevated PVR (4-8 Wood units), perform a staged transcatheter closure by implanting a fenestrated closure device first to reduce the amount of initial shunting. Perform full closure after improvement of RV function and a decrease in PVR a couple of months later in a second step. Markedly elevated baseline PVR values above 8 Wood units usually form a contraindication for closure, as this would deteriorate RV function even further.</li>
	</ol>
	</li>
</ol>
3. 2D transthoracic echocardiography imaging for the interatrial septum
NOTE: The assessment of interatrial septum is recommended according to the 2015 ASE guidelines2. The patient is lying in the left decubitus position with the left arm placed under the head. Standard parasternal, apical and subcostal views are obtained.
<ol>
	<li>Use the subxiphoid frontal four-chamber view; it provides good axial resolution to measure the diameter of the defect along its long axis.&#160;</li>
	<li>Use the subxiphoid sagittal view to visualize the atrial septum along its superior&#8211;inferior axis.</li>
	<li>Use the apical four-chamber view to estimate haemodinamic consequencies of interatrial left to right shunting including RA, RV dilation and RV pressure.</li>
	<li>Use the parasternal short-axis view to measure the aortic and posterior rim of the septal defect.</li>
</ol>
4. 2D/3D Transthoracic Echocardiography Imaging for the anatomical and functional quantification of heart chambers
NOTE: Assessment of atria is recommended according to the consensus statement from the ASE and EACVI on chamber quantification7.
<ol>
	<li>Perform conventional volumetric and functional LA measurement.</li>
	<li>Perform advanced echocardiography techniques using speckle tracking. Optimize acquisition frame rates for speckle tracking to provide the highest frame rate per cardiac cycle without significantly decreasing spatial resolution.
	<ol>
		<li>In the 2D LA strain curve, set the zero strain reference at the left ventricular end-diastole. Calculate the LA strain values of each phase as the difference of two of these measurements8. LA function is divided into reservoir, conduit and contraction phase.&#160;All considerations made for LA measurements can be applied for RA assessment as well.</li>
	</ol>
	</li>
	<li>Measure the tricuspid annular plane systolic excursion, the RV fractional area change, the Doppler tissue imaging (DTI) S&#8217; velocity, and the RV ejection fraction from 3D volumetric evaluation. Perform 2D speckle tracking analysis with RV strain parameters for the evaluation of RV systolic function9.&#160; 
	NOTE: RV measurements are highly important in case of hemodynamically significant ASD, when RV function can be impaired and significant pulmonary hypertension can occur.</li>
	<li>Obtain electrocardiographically gated full-volume 3D data sets from apical four chamber view for 3D LA, LV and RV volume and function measurement, representing parameters of incremental prognostic value over 2D LA parameters10,11.</li>
	<li>Perform conventional volumetric and functional LV measurements, including LV diastolic function assessment using mitral inflow and annular tissue Doppler imaging. 
	NOTE: In case of diastolic dysfunction, acute heart failure may develope after ASD closure due to LV volume overload.</li>
	<li>Assess LV global longitudinal strain due to its prognostic value. 
	NOTE: However, circumferential and radial strain can be also assessed12,13.</li>
</ol>
5. Transesophageal echocardiography imaging for the interatrial septum
<ol>
	<li>Perform TEE examination in patients clinically suitable for potential percutaneous device closure to assess technical feasibility of the closure as well. Otherwise, perform TTE examination or transcranial doppler (TCD) using agitated saline to prove the presence of an interatrial shunt2,14,15,16. Informed written patient consent is mandatory before TEE examination.</li>
	<li>Position the patient on the left lateralis decubitus in case of preoperative screening TEE and on the back position in case of intraoperative TEE. Ensure that patients fast for at least 4 h and remove dental fixtures.</li>
	<li>Use topical oropharyngeal anesthesia (such as lidocaine) and intravenous sedatives (such as midazolam, typical dose 1-5mg) before screening TEE. The intraoperative guiding TEE is performed usually under general anaesthesia.</li>
	<li>Monitor ECG, blood pressure and oxygen saturation. Furthermore, availability and experience with resuscitation equipment is mandatory.</li>
	<li>Define the number, size and location of defects as well as the surrounding atrial septal tissue (rims) and the presence of atrial septal aneurysm. Determine the hemodynamic consequences of atrial septal defects using conventional 2D TEE views, of which midesophageal bicaval and aortic valve short axis view are the most important (Figure 2).</li>
	<li>Verify communication through the foramen using agitated saline contrast during the Valsalva maneuver, when the right atrial pressure temporarily increases, the overlapping septum primum and secundum opens, and the bubbles can cross the canal of PFO from the right atria to the left atria within 3 cardiac cycles. 
	NOTE: The amount of crossing bubbles depends on the size of PFO. A large (grade III) shunt is defined when the number of bubbles exceeds 20.</li>
	<li>Use 3D TEE acquisition methods mainly from the midesophageal short axis view or the bicaval view. Use the narrow-angled (zoomed) and wide-angled (full volume) mode to obtain additional information on the complex and dynamic anatomy of interatrial septum. Measure the size of atrial septal defect at the atrial end-diastole and end-systole in en face views from either the RA or LA (Figure 3).</li>
	<li>Use intraoperative transesophageal echocardiography to guide all steps of the procedure mainly from midesophageal bicaval and short axis view, including advancing the guidewire through the PFO tunnel or ASD and closure device delivery (Figure 1, Figure 4, Figure 5).</li>
	<li>Perform balloon sizing of the stretched diameter of ASD using fluoroscopy and TEE as well. 
	NOTE: The maximum size of the closure device is 90% of the atrial septal length; nevertheless, the ratio of the device to defect should not exceed 2:1 (Figure 6).</li>
	<li>Before the delivery system detachment, evaluate the presence of the residual shunt evaluation and measure the atrial septal tissue rim and atrial roof to closure device distance using a four chamber, short axis and bicaval TEE view.</li>
</ol>
6. Postoperative follow-up
<ol>
	<li>Perform the TTE study before hospital discharge and repeat within 1 month to assess device position, residual shunt and pericardial effusion due to device errosion.</li>
	<li>Perform TTE examination and 12-lead electrocardiography follow up studies at 6, and 12 months, with a subsequent evaluation every year.
	<ol>
		<li>Measure conventional Doppler parameters to evaluate the effect of transcatheter ASD closure on left-sided chambers.</li>
		<li>Measure atrial and ventricular volumetric changes and longitudinal strain parameters are measured in order to track cardiac remodelling (Figure 7, Figure 8). Atrial arrhythmias occur mainly within 1 month after device deployment17.</li>
	</ol>
	</li>
</ol>

<ol>
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E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=et+al.Guidelines+for+the+Echocardiographic+Assessment+of+Atrial+Septal+Defect+and+Patent+Foramen+Ovale:+From+the+American+Society+of+Echocardiography+and+Society+for+Cardiac+Angiography+and+Interventions.">et al.Guidelines for the Echocardiographic Assessment of Atrial Septal Defect and Patent Foramen Ovale: From the American Society of Echocardiography and Society for Cardiac Angiography and Interventions.</a> Journal of the American Society of Echocardiography. 28 (8), 910-958 (2015).</li><li>Saric, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Guidelines+for+the+Use+of+Echocardiography+in+the+Evaluation+of+a+Cardiac+Source+of+Embolism.">Guidelines for the Use of Echocardiography in the Evaluation of a Cardiac Source of Embolism.</a> Journal of the American Society of Echocardiography. 29 (1), 1-42 (2016).</li><li>Krumsdorf, U., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Incidence+and+clinical+course+of+thrombus+formation+on+atrial+septal+defect+and+patient+foramen+ovale+closure+devices+in+1,000+consecutive+patients.">Incidence and clinical course of thrombus formation on atrial septal defect and patient foramen ovale closure devices in 1,000 consecutive patients.</a> Journal of the American College of Cardiology. 43 (2), 302-309 (2004).</li><li>Canpolat, U., G&#252;rses, K. 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P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Standardization+of+left+atrial,+right+ventricular,+and+right+atrial+deformation+imaging+using+two-dimensional+speckle+tracking+echocardiography:+a+consensus+document+of+the+EACVI/ASE/Industry+Task+Force+to+standardize+deformation+imaging.">Standardization of left atrial, right ventricular, and right atrial deformation imaging using two-dimensional speckle tracking echocardiography: a consensus document of the EACVI/ASE/Industry Task Force to standardize deformation imaging.</a> European Heart Journal of Cardiovascular Imaging. 19 (6), 591-600 (2018).</li><li>Hayashi, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Optimal+Analysis+of+Left+Atrial+Strain+by+Speckle+Tracking+Echocardiography:+P-wave+versus+R-wave+Trigger.">Optimal Analysis of Left Atrial Strain by Speckle Tracking Echocardiography: P-wave versus R-wave Trigger.</a> Echocardiography. 32 (8), 1241-1249 (2015).</li><li>Rudski, L. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Guidelines+for+the+echocardiographic+assessment+of+the+right+heart+in+adults:+a+report+from+the+American+Society+of+Echocardiography+endorsed+by+the+European+Association+of+Echocardiography,+a+registered+branch+of+the+European+Society+of+Cardiology,+and+the+Canadian+Society+of+Echocardiography.">Guidelines for the echocardiographic assessment of the right heart in adults: a report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography.</a> Journal of the American Society of Echocardiography. 23 (7), 685-713 (2010).</li><li>Wu, V. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prognostic+value+of+LA+volumes+assessed+by+transthoracic+3D+echocardiography:+comparison+with+2D+echocardiography.">Prognostic value of LA volumes assessed by transthoracic 3D echocardiography: comparison with 2D echocardiography.</a> Journal of the American College of Cardiology: Cardiovascular Imaging. 6 (10), 1025-1035 (2013).</li><li>Badano, L. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Left+Atrial+Volumes+and+Function+by+Three-Dimensional+Echocardiography:+Reference+Values,+Accuracy,+Reproducibility,+and+Comparison+With+Two-Dimensional+Echocardiographic+Measurements.">Left Atrial Volumes and Function by Three-Dimensional Echocardiography: Reference Values, Accuracy, Reproducibility, and Comparison With Two-Dimensional Echocardiographic Measurements.</a> Circulation: Cardiovascular Imaging. 9 (7), (2016).</li><li>Edvardsen, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+year+2015-16+in+the+European+Heart+Journal-Cardiovascular+Imaging.+Part+II.">The year 2015-16 in the European Heart Journal-Cardiovascular Imaging. Part II.</a> European Heart Journal: Cardiovascular Imaging. 18 (12), 1322-1330 (2017).</li><li>Galderisi, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Standardization+of+adult+transthoracic+echocardiography+reporting+in+agreement+with+recent+chamber+quantification,+diastolic+function,+and+heart+valve+disease+recommendations:+an+expert+consensus+document+of+the+European+Association+of+Cardiovascular+Imaging.">Standardization of adult transthoracic echocardiography reporting in agreement with recent chamber quantification, diastolic function, and heart valve disease recommendations: an expert consensus document of the European Association of Cardiovascular Imaging.</a> Europen Heart Journal: Cardiovascular Imaging. 18 (12), 1301-1310 (2017).</li><li>Marriott, K., Manins, V., Forshaw, A., Wright, J., Pascoe, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Detection+of+right-to-left+atrial+communication+using+agitated+saline+contrast+imaging:+experience+with+1162+patients+and+recommendations+for+echocardiography.">Detection of right-to-left atrial communication using agitated saline contrast imaging: experience with 1162 patients and recommendations for echocardiography.</a> Journal of the American Society of Echocardiography. 26 (1), 96-102 (2013).</li><li>Mojadidi, M. K., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=et+al+Accuracy+of+conventional+transthoracic+echocardiography+for+the+diagnosis+of+intracardiac+right-to-left+shunt:+a+meta-analysis+of+prospective+studies.">et al Accuracy of conventional transthoracic echocardiography for the diagnosis of intracardiac right-to-left shunt: a meta-analysis of prospective studies.</a> Echocardiography. 31 (9), 1036-1048 (2014).</li><li>Mojadidi, M. K., Bogush, N., Caceres, J. D., Msaouel, P., Tobis, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diagnostic+accuracy+of+transesophageal+echocardiogram+for+the+detection+of+patent+foramen+ovale:+a+meta-analysis.">Diagnostic accuracy of transesophageal echocardiogram for the detection of patent foramen ovale: a meta-analysis.</a> Echocardiography. 31 (6), 752-758 (2014).</li><li>Staubach, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=New+onset+atrial+fibrillation+after+patent+foramen+ovale+closure.">New onset atrial fibrillation after patent foramen ovale closure.</a> Catheter and Cardiovascular Interventions. 74 (6), 889-895 (2009).</li><li>Singh, H. S., Katchi, F., Naidu, S. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=PFO+Closure+for+Cryptogenic+Stroke:+A+Review+and+Clinical+Treatment+Algorithm.">PFO Closure for Cryptogenic Stroke: A Review and Clinical Treatment Algorithm.</a> Cardiology in Review. 25 (4), 147-157 (2017).</li><li>Sanna, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cryptogenic+stroke+and+underlying+atrial+fibrillation.">Cryptogenic stroke and underlying atrial fibrillation.</a> New England Journal of Medicine. 370 (26), 2478-2486 (2014).</li><li>Prefasi, D., Mart&#237;nez-S&#225;nchez, P., Fuentes, B., D&#237;ez-Tejedor, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+utility+of+the+RoPE+score+in+cryptogenic+stroke+patients+&#8804;50+years+in+predicting+a+stroke-related+patent+foramen+ovale.">The utility of the RoPE score in cryptogenic stroke patients &#8804;50 years in predicting a stroke-related patent foramen ovale.</a> International Journal of Stroke. 11 (1), 7-8 (2016).</li><li>Yamano, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=et+al+Appropriate+selection+of+echocardiographic+guidance+for+transcatheter+atrial+septal+defect+closure.">et al Appropriate selection of echocardiographic guidance for transcatheter atrial septal defect closure.</a> International Journal of Cardiovascular Imaging. 36 (5), 855-863 (2020).</li><li>Oto, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Transthoracic+echocardiography+guidance+during+percutaneous+closure+of+patent+foramen+ovale.">Transthoracic echocardiography guidance during percutaneous closure of patent foramen ovale.</a> Echocardiography. 28 (10), 1074-1080 (2011).</li></ol>

Authors declare no conflict of interest.&#160;

Careful patient selection for transcatheter PFO closure represents one of the most challanging steps of the clinical evaluation, as ruling out atrial fibrillation can be difficult. Several trials in the past few years have suggested greater yield with longer term monitoring to detect atrial fibrillation.18 The Cryptogenic Stroke and Underlying Atrial Fibrillation (CRYSTAL-AF) trial detected increased atrial fibrillation rate in the insertable cardiac monitor group (8,9%) compared with standard mon...

Patent Foramen Ovale (PFO) is not a true tissue deficiency of atrial septum; it is present in about 20-25% of&#160;the adult population, and in most cases it does not have any clinical significance (Figure 1). Cryptogenic stroke accounts for ~30% of ischemic strokes and is defined as a&#160;condition without an apparent cause at the early inpatient work-up. Patients under 45 years of age represent 10% of stroke burden with as much as 40% defined as cryptogenic. Secondary prevention of stroke using transcatheter closure technique remains paramount in reducing morbidity and mortality1.
Atrial septal defects (ASDs) include different lesions on different atrial septum locations, resulting in shunting. The most common form is ostium secundum ASD, usually optimal for percutan devise closure. ASDs are generally discovered during the workup of right ventricular (RV) dysfunction and/or dilatation, and rarely after a suspected paradoxical embolism or cryptogenic stroke2,3.
Transthoracic (TTE) and transesophageal (TEE) echocardiography is performed for qualitative and quantitative assessment of atrial septum deficiencies. Three dimensional (3D) TEE provides more in depth information of the interatrial septum, and it gives more precise imaging of catheters and the closure device during intraoperative guiding. Postoperative follow up evaluations with TTE should be performed at 1, 6, and 12 months after the procedure, with a subsequent evaluation every year to assess device position, residual shunts, pericardial effusion, changes in size and function of the cardiac chambers and pulmonary circulation. Further advanced echocardiography techniques using speckle tracking echocardiography may help to understand potential functional left atrial remodeling following percutaneous closure and its impact on atrial arrhythmias2.

<table><tbody><tr><td>TomTec Imaging workstation</td><td>TomTec Imaging, Unterschleissheim, Germany</td><td></td><td>4D LALV Function analysing software</td></tr><tr><td>Ultrasound machine</td><td>Philips Epiq CvX</td><td>serial number US81881251</td><td>X5-1 and X7 transducers</td></tr><tr><td>Wiwe external ECG single chanel recorder</td><td>Sanat Metal</td><td>5-810-200-1611</td><td>external ECG single chanel recorder</td></tr></tbody></table>

echocardiographic evaluation of atrial communications before transcatheter closure

Transthoracic (TTE) and transesophageal echocardiography (TEE) is the standard imaging method for atrial septal defect (ASD) and patent foramen ovale (PFO) detection, for patient selection for transcatheter ASD/PFO closure,&#160;for intraoperative guidance and for long-term follow-up. The size, shape, location and the number of the atrial communications schould be determined. The accuracy of PFO detection can be improved by using agitated saline together with maneuvers to transiently increase the right atrial (RA) pressure. The appearance of microbubbles in the left atrium (LA) within 3 cardiac cycles after opacification of the RA is considered positive for the presence of an intracardiac shunt. Three dimensional TEE identifies further septal fenestrations and describes the dynamic morphology of ASD/PFO and atrial septal aneurysm. Follow-up evaluations with TTE is recommended at 1, 6, and 12 months after the procedure, with a subsequent evaluation every year. Previous studies showed an increased incidence of atrial arrhythmias early after device closure. Speckle tracking analysis may help to understand functional left atrial remodeling following percutaneous closure and its impact on atrial arrhythmias.

Clinical evaluation of symptomatic, 41 years old female patient revealed ostium secundum type ASD and floppy atrial septum using TTE and TEE examination 
TTE examination showed right ventricular and biatrial enlargement with elevated pulmonary artery systolic pressure. TEE examination was used to estimate the size and shape of ASD using 2D and 3D methods. 2D, 3D native and balloon sizing TEE measurements were compared (Figure 4, Figure 5, <...

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Echocardiographic Evaluation of Atrial Communications before Transcatheter Closure

Transthoracic (TTE) and transesophageal (TEE) echocardiography represent the basic imaging tools for interatrial septum examination. Three dimensional (3D) TEE provides incremental information in the assessment of the interatrial septum. Further advanced echocardiography techniques using speckle tracking echocardiography are applied for sensitive volumetric and functional assessment of the heart chambers.&#160;

Transthoracic (TTE) and transesophageal echocardiography (TEE) is the standard imaging method for atrial septal defect (ASD) and patent foramen ovale ...

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3.6K Views.  Semmelweis University. Transthoracale en transesofhagaël gezondheidscardiografie is de standaard beeldvormingsmethode om interatriale septumdeficiënties op te sporen, patiënten te selecteren voor transkathetersluiting, de interatriale procedure te begeleiden en de patiënten op te volgen. Dus met dimensionale, transesofageale echocardiografie biedt een meer diepgaande informatie van het interatriale septum dat de grootte, vorm, locatie en het aantal van de interatriale communicatie bepaalt. Driedimensionale echo...

Video: Echocardiographic Evaluation of Atrial Communications before Transcatheter Closure

Catheter Ablation in Combination With Left Atrial Appendage Closure for Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide 1-3. The rapid, irregular, and disordered electrical activity in the atria gives rise to palpitations, fatigue, dyspnea, chest pain and dizziness with or without syncope 4, 5. Patients with AF have a five-fold higher risk of stroke 6.
Oral anticoagulation (OAC) with warfarin is commonly used for stroke prevention in patients with AF and has been shown to reduce the risk of stroke by 64% 7. Warfarin therapy has several major disadvantages, however, including bleeding, non-tolerance, interactions with other medications and foods, non-compliance and a narrow therapeutic range 8-11. These issues, together with poor appreciation of the risk-benefit ratio, unawareness of guidelines, or absence of an OAC monitoring outpatient clinic may explain why only 30-60% of patients with AF are prescribed this drug 8.
The problems associated with warfarin, combined with the limited efficacy and/or serious side effects associated with other medications used for AF 12,13, highlight the need for effective non-pharmacological approaches to treatment. One such approach is catheter ablation (CA), a procedure in which a radiofrequency electrical current is applied to regions of the heart to create small ablation lesions that electrically isolate potential AF triggers 4. CA is a well-established treatment for AF symptoms 14, 15, that may also decrease the risk of stroke. Recent data showed a significant decrease in the relative risk of stroke and transient ischemic attack events among patients who underwent ablation compared with those undergoing antiarrhythmic drug therapy 16.
Since the left atrial appendage (LAA) is the source of thrombi in more than 90% of patients with non-valvular atrial fibrillation 17, another approach to stroke prevention is to physically block clots from exiting the LAA. One method for occluding the LAA is via percutaneous placement of the WATCHMAN LAA closure device. The WATCHMAN device resembles a small parachute. It consists of a nitinol frame covered by fabric polyethyl terephthalate that prevents emboli, but not blood, from exiting during the healing process. Fixation anchors around the perimeter secure the device in the LAA (Figure 1). To date, the WATCHMAN is the only implanted percutaneous device for which a randomized clinical trial has been reported. In this study, implantation of the WATCHMAN was found to be at least as effective as warfarin in preventing stroke (all-causes) and death (all-causes) 18. This device received the Conformit&eacute; Europ&eacute;enne (CE) mark for use in the European Union for warfarin eligible patients and in those who have a contraindication to anticoagulation therapy 19.
Given the proven effectiveness of CA to alleviate AF symptoms and the promising data with regard to reduction of thromboembolic events with both CA and WATCHMAN implantation, combining the two procedures is hoped to further reduce the incidence of stroke in high-risk patients while simultaneously relieving symptoms. The combined procedure may eventually enable patients to undergo implantation of the WATCHMAN device without subsequent warfarin treatment, since the CA procedure itself reduces thromboembolic events. This would present an avenue of treatment previously unavailable to patients ineligible for warfarin treatment because of recurrent bleeding 20 or other warfarin-associated problems.
The combined procedure is performed under general anesthesia with biplane fluoroscopy and TEE guidance. Catheter ablation is followed by implantation of the WATCHMAN LAA closure device. Data from a non-randomized trial with 10 patients demonstrates that this procedure can be safely performed in patients with a CHADS2 score of greater than 1 21. Further studies to examine the effectiveness of the combined procedure in reducing symptoms from AF and associated stroke are therefore warranted.

Catheter ablation is combined with placement of the WATCHMAN Left Atrial Appendage Closure Device to prevent ischemic stroke in a patient with non-valvular atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, affecting millions of individuals worldwide 1-3. The rapid, irregular, and ...

Non-fluoroscopic Catheter Tracking for Fluoroscopy Reduction in Interventional Electrophysiology

A technological platform (MediGuide) has been recently introduced for non-fluoroscopic catheter tracking. In several studies, we have demonstrated that the application of this non-fluoroscopic catheter visualization system (NFCV) reduces fluoroscopy time and dose by 90-95% in a variety of electrophysiology (EP) procedures. This can be of relevance not only to the patients, but also to the nurses and physicians working in the EP lab. Furthermore, in a subset of indications such as supraventricular tachycardias, NFCV enables a fully non-fluoroscopic procedure and allows the lab staff to work without wearing lead aprons. With this protocol, we demonstrate that even complex procedures such as ablations of atrial fibrillation, that are typically associated with fluoroscopy times of &#62;30 min in conventional settings, can safely be performed with a reduction of &#62;90% in fluoroscopy exposure by the additional use of NFCV.

Radiation exposure is an underestimated risk in complex ablation procedures. Here, we describe a protocol to significantly decrease fluoroscopy time and dosage for both the patient and the lab staff by using a novel non-fluoroscopic catheter visualization system.

A technological platform (MediGuide) has been recently introduced for non-fluoroscopic catheter tracking. In several studies, we have demonstrated that ...

Reduction of Iatrogenic Atrial Septal Defects with an Anterior and Inferior Transseptal Puncture Site when Operating the Cryoballoon Ablation Catheter

The cryoballoon catheter ablates atrial fibrillation (AF) triggers in the left atrium (LA) and pulmonary veins (PVs) via transseptal access. The typical transseptal puncture site is the fossa ovalis (FO) &#8211; the atrial septum&#8217;s thinnest section. A potentially beneficial transseptal site, for the cryoballoon, is near the inferior limbus (IL). This study examines an alternative transseptal site near the IL, which may decrease the frequency of acute iatrogenic atrial septal defect (IASD). Also, the study evaluates the acute pulmonary vein isolation (PVI) success rate utilizing the IL location. 200 patients were evaluated by retrospective chart review for acute PVI success rate with an IL transseptal site. An additional 128 IL transseptal patients were compared to 45 FO transseptal patients by performing Doppler intracardiac echocardiography (ICE) post-ablation to assess transseptal flow after removal of the transseptal sheath. After sheath removal and by Doppler ICE imaging, 42 of 128 (33%) IL transseptal patients demonstrated acute transseptal flow, while 45 of 45 (100%) FO transseptal puncture patients had acute transseptal flow. The difference in acute transseptal flow detection between FO and IL sites was statistically significant (P &#60;0.0001). Furthermore, 186 of 200 patients (with an IL transseptal puncture) did not need additional ablation(s) and had achieved an acute PVI by a &#8220;cryoballoon only&#8221; technique. An IL transseptal puncture site for cryoballoon AF ablations is an effective location to mediate PVI at all four PVs. Additionally, an IL transseptal location can lower the incidence of acute transseptal flow by Doppler ICE when compared to the FO. Potentially, the IL transseptal site may reduce later IASD complications post-cryoballoon procedures.

The goal of this study is to demonstrate the preferential location of transseptal puncture during a cryoballoon catheter ablation procedure for the treatment of atrial fibrillation.

The cryoballoon catheter ablates atrial fibrillation (AF) triggers in the left atrium (LA) and pulmonary veins (PVs) via transseptal access. The typical ...

Three-Dimensional Echocardiographic Method for the Visualization and Assessment of Specific Parameters of the Pulmonary Veins

The dimensions of the pulmonary veins are important parameters when planning pulmonary vein isolation (PVI), especially with the cryoballoon ablation technique. Acknowledging the dimensions and anatomical variations of the pulmonary veins (PVs) may improve the outcome of the intervention. Conventional 2D transoesophageal echocardiography can only provide limited data about the dimensions of the PVs; however, 3D echocardiography can further evaluate relevant diameters and areas of the PVs, as well as their spatial relationship to surrounding structures. In previous literature data, parameters influencing the success rate of PVI have already been identified. These are the left lateral ridge, the intervenous ridge, the ostial area of the PVs and the ovality index of the ostium. Proper imaging of the PVs by 3D echocardiography is a technically challenging method. One crucial step is the collection of images. Three individual transducer positions are necessary to visualize the important structures; these are the left lateral ridge, the ostium of the PVs and the intervenous ridge of the left and right PVs. Next, 3D images are acquired and saved as digital loops. These datasets are cropped, which result in the en face views displaying spatial relationships. This step can also be employed to determine the anatomical variations of the PVs. Finally, multiplanar reconstructions are created to measure each individual parameter of the PVs.
Optimal quality and orientation of the acquired images are paramount for the appropriate assessment of PV anatomy. In the present work, we examined the 3D visibility of the PVs and the suitability of the above method in 80 patients. The aim was to provide a detailed outline of the essential steps and potential pitfalls of PV visualization and assessment with 3D echocardiography.

The dimensions of the pulmonary veins (PV) are important parameters when planning pulmonary vein isolation. 2D transoesophageal echocardiography can only provide limited data about the PVs; however, 3D echocardiography can evaluate relevant diameters and areas of the PVs, as well as their spatial relationship to surrounding structures.

The dimensions of the pulmonary veins are important parameters when planning pulmonary vein isolation (PVI), especially with the cryoballoon ablation ...

Bioengineering

Electrophysiological Assessment of Murine Atria with High-Resolution Optical Mapping

Recent genome-wide association studies targeting atrial fibrillation (AF) have indicated a strong association between the genotype and electrophysiological phenotype in the atria. That encourages us to utilize a genetically-engineered mouse model to elucidate the mechanism of AF. However, it is difficult to evaluate the electrophysiological properties in murine atria due to their small size. This protocol describes the electrophysiological evaluation of atria using an optical mapping system with a high temporal and spatial resolution in Langendorff perfused murine hearts. The optical mapping system is assembled with dual high-speed complementary metal oxide semiconductor cameras and high magnification objective lenses, to detect the fluorescence of a voltage-sensitive dye and Ca2+ indicator. To focus on the assessment of murine atria, optical mapping is performed with an area of 2 mm &#215; 2 mm or 10 mm x 10 mm, with a 100 &#215; 100 resolution (20 &#181;m/pixel or 100 &#181;m/pixel) and sampling rate of up to 10 kHz (0.1 ms) at maximum. A 1-French size quadripolar electrode pacing catheter is placed into the right atrium through the superior vena cava avoiding any mechanical damage to the atrium, and pacing stimulation is delivered through the catheter. An electrophysiological study is performed with programmed stimulation including constant pacing, burst pacing, and up to triple extrastimuli pacing. Under a spontaneous or pacing rhythm, the optical mapping recorded the action potential duration, activation map, conduction velocity, and Ca2+ transient individually in the right and left atria. In addition, the programmed stimulation also determines the inducibility of atrial tachyarrhythmias. Precise activation mapping is performed to identify the propagation of the excitation in the atrium during an induced atrial tachyarrhythmia. Optical mapping with a specialized setting enables a thorough electrophysiological evaluation of the atrium in murine pathological models.

This protocol describes the electrophysiological evaluation of murine atria utilizing an optical mapping system with a high temporal and spatial resolution, including dual recordings of the membrane voltage and Ca2+ transient under programmed stimulation through a specialized electrode catheter.

Recent genome-wide association studies targeting atrial fibrillation (AF) have indicated a strong association between the genotype and ...

Cox-Maze IV Procedure Concomitant with Valvular Surgery In Situs Inversus Dextrocardia: A Single-Center Experience in China

Atrial fibrillation (AF) is the most common cardiac arrhythmia. The use of ablation technologies made the Cox-Maze IV procedure (CMP-IV) technically easier, faster, becoming the gold standard for the surgical treatment of AF. However, the efficacy and safety of CMP-IV in situs inversus dextrocardia are largely unknown. This paper summarizes the CMP-IV procedure performed concomitantly with valvular surgery in patients with situs inversus dextrocardia at this institution.
From February 2016 to September 2020, three dextrocardia patients with persistent AF and valvular diseases were referred to this institution for valvular and CMP-IV surgery. CMP-IV was performed using either cryoablation with a nitrous oxide (N2O)-based cryoprobe or a bipolar radiofrequency clamp and bipolar radiofrequency pen. Mechanical valve replacement or mitral vavuloplasty was performed in another patient in addition to tricuspid annuloplasty. Transmurality of the ablated atrial tissues was evaluated by electron microscopy. Heart function was assessed by transthoracic echocardiography. Cardiac rhythm was monitored by 24 h Holter at 3, 6, 12, 18, 24, and 48 months follow-up. 
All the AF was successfully eliminated in the ablation procedure without recurrence or other complications during hospitalization. The mean bypass and crossclamp times were similar in all the patients. The postoperative ventilator support time, the duration of stay in the ICU, and postoperative residence time were also not significantly different among the patients. Transmural atrial necrosis was detected in the ablated atrial tissues. Sinus rhythm maintenance was achieved at 3, 6, 12, 18, 24, and 48 months follow-up in all the patients. All valve protheses switched freely; no tricuspid regurgitation was observed. The results of the present study demonstrate that the CMP-IV is safe and effective in eliminating AF in dextrocardia patients concomitant with valvular surgery.

We summarize the Cox-Maze IV procedure concomitant with valvular surgery performed in patients with situs inversus dextrocardia at this institution.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. The use of ablation technologies made the Cox-Maze IV procedure (CMP-IV) technically ...

Estimating Bilateral Atrial Function by Cardiovascular Magnetic Resonance Feature Tracking in Patients with Paroxysmal Atrial Fibrillation

Atrial fibrillation (AF) is the most common form of arrhythmia. Atrial remodeling is considered the most critical mechanism for the presence and development of atrial fibrillation. Also, atrial remodeling can lead to the enlargement and dysfunction of the left atrium (LA), resulting in thrombosis and heart failure. Functional changes in left atrial strain and strain rate occur before structural alterations and are closely associated with structural remodeling and left atrial fibrosis. These parameters are sensitive biomarkers for atrial function. Cardiac magnetic resonance feature tracking (CMR-FT) is a novel, non-invasive, post-processing technique that can evaluate left atrial strain and strain rate. The CMR-FT was utilized in this investigation to assess the bilateral atrium strain rate in individuals with paroxysmal AF. Modifications in each segmental strain were evaluated using segmental analysis. The CMR-FT is recommended for non-invasive evaluations in the clinical assessment of atrial strain among existing strain imaging techniques. Further, it is a flexible parameter measurement with good reproducibility, high soft-tissue resolution, and post-processing based on standard cine balanced steady-state free precision (bSSFP) long-axis images without requiring a new sequence acquisition.

The atrial function is associated with the strain and strain rate. The cardiac magnetic resonance feature tracking (CMR-FT) technique was used in this study to quantify left and right atrial global and segmental longitudinal strain and strain rate in individuals with paroxysmal atrial fibrillation.

Atrial fibrillation (AF) is the most common form of arrhythmia. Atrial remodeling is considered the most critical mechanism for the presence and ...

Closure of a Patent Foramen Ovale (PFO): An Intervention Sequence

A patent foramen ovale (PFO) persists in about one-quarter of people and is the source of up to 25% of all ischemic strokes, especially strokes in young adults. PFO can be easily diagnosed by transthoracic contrast and/or transesophageal echocardiography. Interventional closure of the PFO via the femoral vein is a commonly used cardiological procedure since several trials have demonstrated the superiority of PFO closure over standard medical therapy in patients with PFO and who have experienced post ischemic, cardioembolic, or cryptogenic stroke. The current paper and video show the procedure of PFO closure in a step-by-step manner.

Closure of a Patent Foramen Ovale PFO: An Intervention Sequence

The closure of a patent foramen ovale (PFO) is a catheter-based intervention to prevent PFO-associated stroke. The PFO-occlusion device is advanced through the femoral vein and deployed across the interatrial septum using transesophageal echocardiography (TEE) and fluoroscopic guidance. The following protocol provides a step-by-step guide for the PFO-closure intervention using a double-disc device.

A patent foramen ovale (PFO) persists in about one-quarter of people and is the source of up to 25% of all ischemic strokes, especially strokes in young ...

ICE-Based 3D Remodeling for the Left Atrium and Pulmonary Vein

Three-Dimensional Modeling of the Left Atrium and Pulmonary Veins with a Precise Intracardiac Echocardiography Approach

Intracardiac echocardiography (ICE) is a novel tool for estimating cardiac anatomy during pulmonary vein isolation procedures, particularly the left atrium (LA) anatomy and pulmonary vein structures. ICE is widely used to establish a three-dimensional (3D) left atrial structural model during ablation procedures. However, it is unclear whether using ICE in a precise 3D modeling method can provide a more accurate left atrial 3D model and the transseptal approach. This study proposes a protocol to model the left atrium and pulmonary veins with ICE and fast anatomical mapping (FAM) catheter remodeling. It evaluates the accuracy of the models produced using the two methods through observer scoring. We included 50 patients who underwent ICE-based 3D remodeling and 45 who underwent FAM 3D remodeling based on pulmonary vein isolation procedures. The pulmonary vein antrum remodeling is estimated by comparing the antrum area acquired by remodeling and left atrial computed tomography angiography (CTA). The observer scores for the modeling in the ICE and FAM groups were 3.40 &#177; 0.81 and 3.02 &#177; 0.72 (P &#60; 0.05), respectively. The pulmonary vein antrum area obtained using the ICE- and FAM-based methods showed a correlation with the area acquired by left atrium CT. However, the 95% confidence interval bias was narrower in ICE-acquired models than in FAM-acquired models (-238 cm2 to 323 cm2 Vs. -363 cm2 to 386 cm2, respectively) using Bland-Altman analysis. Therefore, precise ICE possesses high accuracy in estimating the left atrial structure, becoming a promising approach for future cardiac structure estimation.

Author Spotlight: Advancements in Intracardiac Echocardiography for Atrial Anatomy Assessment 

Accurate intracardiac echocardiography (ICE) shows significant accuracy in estimating the left atrial structure, a prospective and promising cardiac structure estimation method. Here we propose a protocol for three-dimensional modeling of the left atrium and pulmonary veins with ICE and fast anatomical mapping (FAM) catheter remodeling.

Intracardiac echocardiography (ICE) is a novel tool for estimating cardiac anatomy during pulmonary vein isolation procedures, particularly the left ...

Optimizing Pulmonary Artery Banding for Consistent Right Heart Failure Induction

Rat Model of Right-Sided Cardiac Remodeling and Arrhythmia Using Pulmonary Artery Banding

Clinical conditions, including chronic obstructive pulmonary disease or pulmonary arterial hypertension (PAH), can lead to chronic right ventricle pressure overload and progressive right heart failure (RHF). RHF can be identified by right-sided cardiac hypertrophy and dilation associated with abnormal myocardial function affecting the RV and the right atrium (RA). We recently demonstrated that severe RHF is accompanied by an increased risk of atrial inflammation, atrial fibrosis, and atrial fibrillation (AF), the most common type of cardiac arrhythmia (CA). Recent studies have shown that RV and RA inflammation plays an important role in the arrhythmogenesis of CA, including AF. However, the impact of inflammation in the development of CA and AF in RHF is poorly described.
Experimental models of RHF are required to better understand the association between right-sided myocardial inflammation and CA. The rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH) is well-established to provoke RHF. However, MCT triggers severe pneumo-toxicity and pulmonary inflammation. Hence, MCT-induced RHF does not help to distinguish whether the subsequent myocardial inflammation originates from the RHF per se or circulating inflammatory signals secreted by the injured lung.
In this article, a mechanical method involving pulmonary artery trunk banding (PAB) was used to provoke right-sided cardiac arrhythmogenesis. The PAB consists of performing a permanent suture of the pulmonary artery trunk for 3 weeks. Such an approach generates increased right-sided pressure overload. At D21 post-PAB, the suture results in hypertrophied, dilated, and inflamed RV and RA. The PAB-induced RHF is also accompanied by vulnerability to ventricular and atrial arrhythmias, including AF.

Right heart failure (RHF) is characterized by right-sided cardiac dilation and hypertrophy, leading to ventricular and atrial malfunction. Cardiopulmonary conditions associated with RHF are accompanied by an increased risk for cardiac arrhythmias. This article describes a standardized model of pulmonary artery banding-induced RHF associated with enhanced ventricular and atrial arrhythmogenesis.

Echocardiographic Evaluation of Atrial Communications before Transcatheter Closure

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